This collaborative research project will combine electrophysiological recordings from olfactory receptor neurons (ORN) of genetically modified mouse lines with computational modeling of the (slow) signal transduction cascade and (fast) action potential generation. In doing so, the researchers aim to develop a refined mathematical description regarding the molecular basis for olfactory transduction and adaptation within vertebrate ORNs. This is an important goal not only because olfaction shapes animal behavior and social ecology but also because similar molecular mechanisms are implicated in olfactory disease. One of the current challenges in neuroscience research is bridging the temporal scales of biochemical and neural processes. Olfaction provides a convenient model system for studying how single neurons can leverage the timing of molecular events to process information. Subsequent to odor presentation, a G-protein-coupled signal transduction cascade is activated within the ORN cilia leading to current influx. Ultimately, ORNs generate action potentials, which are the primary information transmitted to the olfactory bulb. A successful model of the ORN must, therefore, be able to illustrate and predict the molecular processes underlying both the slow (transduction) and fast (action potential) currents during stimulation. The applicants' model is unique among the existing models in its ability to accurately predict the adaptive responses of ORNs to repetitive stimuli, the oscillatory responses during sustained stimulation, and the desensitization following a single brief odorant pulse. This model has recently been expanded to include the generation of action potentials. Mutant mouse lines, which are currently available and will be created, will be used to probe the relation of these components to transduction activity through computational modeling of electrophysiological recordings of the mutant ORNs. [unreadable] [unreadable] [unreadable]